This combined proposal extends our investigations in the following areas: 1. Hereditary bovine protoporphyria studies will emphasize the nature and significance of the ferrochelatase defect. Appearance of fluorescence in clones of cultured bone marrow cells will be correlated with the stage of erythroid cell development to determine when ferrochelatase activity becomes rate-limiting in this condition, in erythropoietic porphyria, in lead poisoning, etc. 2. Protein-porphyrin binding will be investigated in plasma and tissues of porphyric and other subjects. Similar studies will be done following injection of "hematoporphyrin" (and related compounds) or of naturally occurring porphyrins. 3. Quantitative assays of zinc-bound versus "free" protoporphyrin will be made in blood and tissues of patients, and of animals with porphyria, experimental lead poisoning zinc deficiency, etc. 4. Previous studies on experimental renal porphyria will be extended to include various renal function tests and quantitative assays of renal hemoproteins.